New Developments in the Front‑line Treatment of Advanced Stage Classic Hodgkin Lymphoma: A Canadian Perspective
Abstract
Classic Hodgkin lymphoma (cHL) is highly curable, with excellent outcomes achieved through decades of treatment refinement. Recent years have witnessed a paradigm shift in the management of patients with advanced stage disease, driven by the integration of novel therapies into front-line treatment. Minimizing long-term complications remains an important objective, especially for patients in the adolescent/young adult (AYA) age group. Herein, we summarize the latest developments in the treatment of advanced stage cHL through a Canadian lens, focusing on recent clinical trials that have reshaped the therapeutic landscape.
References
Johnson P, Federico M, Kirkwood A, Fosså A, Berkahn L, Carella A, et al. adapted treatment guided by interim PET-CT scan in advanced Hodgkin’s lymphoma. N Engl J Med. 2016;374(25):2419–29.
Castellino SM, Pei Q, Parsons SK, Hodgson D, McCarten K, Horton T, et al. Brentuximab vedotin with chemotherapy in pediatric high-risk Hodgkin’s lymphoma. N Engl J Med. 2022;387(18):1649–60.
Federico M, Luminari S, Iannitto E, Polimeno G, Marcheselli L, Montanini A, et al. ABVD compared with BEACOPP compared with CEC for the initial treatment of patients with advanced Hodgkin’s lymphoma: results from the HD2000 Gruppo Italiano per lo Studio dei Linfomi trial. J Clin Oncol. 2009;27(5):805–11.
Viviani S, Zinzani PL, Rambaldi A, Brusamolino E, Levis A, Bonfante V, et al. ABVD versus BEACOPP for Hodgkin’s lymphoma when high-dose salvage is planned. N Engl J Med. 2011;365(3):203–12.
Merli F, Luminari S, Gobbi PG, Cascavilla N, Mammi C, Ilariucci F, et al. Long-term results of the HD2000 trial comparing ABVD versus BEACOPP versus COPP-EBV-CAD in untreated patients with advanced Hodgkin lymphoma: a study by Fondazione Italiana Linfomi. J Clin Oncol. 2016;34(11):1175–81.
Gordon LI, Hong F, Fisher RI, Bartlett NL, Connors JM, Gascoyne RD, et al. Randomized Phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advanced-stage Hodgkin lymphoma: an intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496). J Clin Oncol. 2013;31(6):684–91.
Ansell SM, Radford J, Connors JM, Długosz-Danecka M, Kim WS, Gallamini A, et al. Overall survival with brentuximab vedotin in Stage III or IV Hodgkin’s lymphoma. N Engl J Med. 2022;387(4):310–20.
Gallamini A, Barrington SF, Biggi A, Chauvie S, Kostakoglu L, Gregianin M, et al. The predictive role of interim positron emission tomography for Hodgkin lymphoma treatment outcome is confirmed using the interpretation criteria of the Deauville five-point scale. Haematologica. 2014;99(6):1107–13.
Biggi A, Gallamini A, Chauvie S, Hutchings M, Kostakoglu L, Gregianin M, et al. International validation study for interim PET in ABVD-treated, advanced-stage Hodgkin lymphoma: interpretation criteria and concordance rate among reviewers. J Nucl Med. 2013;54(5):683–90.
Gallamini A, Hutchings M, Rigacci L, Specht L, Merli F, Hansen M, et al. Early interim 2-[18F]Fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to international prognostic score in advanced-stage Hodgkin’s lymphoma: a report from a joint Italian-Danish study. J Clin Oncol. 2007;25(24):3746–52.
Gallamini A, Tarella C, Viviani S, Rossi A, Patti C, Mulé A, et al. early chemotherapy intensification with escalated BEACOPP in patients with advanced-stage Hodgkin lymphoma with a positive interim positron emission tomography/computed tomography scan after two ABVD cycles: long-term results of the GITIL/FIL HD 0607 Trial. J Clin Oncol. 2018;36(5):454–62.
Stephens DM, Li H, Schöder H, Straus DJ, Moskowitz CH, LeBlanc M, et al. Five-year follow-up of SWOG S0816: limitations and values of a PET-adapted approach with stage III/IV Hodgkin lymphoma. Blood. 2019;134(15):1238–46.
Ricardi U, Levis M, Evangelista A, Gioia DM, Sacchetti GM, Gotti M, et al. Role of radiotherapy to bulky sites of advanced Hodgkin lymphoma treated with ABVD: final results of FIL HD0801 trial. Blood Adv. 2021;5(21):4504–14.
Gallamini A, Rossi A, Patti C, Picardi M, Romano A, Cantonetti M, et al. Consolidation radiotherapy could be safely omitted in advanced Hodgkin lymphoma with large nodal mass in complete metabolic response after ABVD: final analysis of the randomized GITIL/FIL HD0607 trial. J Clin Oncol. 2020;38(33):3905–13.
LaCasce AS, Dockter T, Ruppert AS, Kostakoglu L, Schöder H, Hsi E, et al. positron emission tomography–adapted therapy in bulky stage I/II classic Hodgkinlymphoma: CALGB 50801 (Alliance). J Clin Oncol. 2022;41(5):1023-34.
Kim JL, Villa D, Tonseth RP, Gerrie AS, Wilson D, Benard F, et al. Long-term follow-up of bulky classic Hodgkin lymphoma managed with ABVD and PET-guided RT demonstrates excellent outcomes in PET-negative cases. Br J Haematol. 2025;206(1):167–71.
Casasnovas RO, Bouabdallah R, Brice P, Lazarovici J, Ghesquieres H, Stamatoullas A, et al. PET-adapted treatment for newly diagnosed advanced Hodgkin lymphoma (AHL2011): a randomised, multicentre, non-inferiority, phase 3 study. Lancet Oncol. 2019;20(2):202–15.
Straus DJ, Długosz-Danecka M, Connors JM, Alekseev S, Illés Á, Picardi M, et al. Brentuximab vedotin with chemotherapy for stage III or IV classical Hodgkin lymphoma (ECHELON-1): 5-year update of an international, open-label, randomised, phase 3 trial. Lancet Haematol. 2021;8(6):e410–21.
Zheng S, Gupta K, Goyal P, Nakajima R, Michaud L, Batlevi CL, et al. outcomes of patients with positive interim positron emission tomography (PET) continuing ABVD in the clinical setting. Cancers. 2023;15(6):1760.
Hamid MS, Rutherford SC, Jang H, Kim S, Patel K, Bartlett NL, et al. outcomes among classical Hodgkin lymphoma patients after an interim PET scan: a real-world experience. Clin Lymphoma Myeloma Leuk. 2022;22(7):e435–42.
Kim JL, Villa D, Tonseth RP, Gerrie AS, Wilson D, Benard F, et al. Evaluation of long-term outcomes in advanced stage classic Hodgkin lymphoma treated with ABVD using a PET-guided strategy. HemaSphere. 2025;9(S1):1135–6.
Luminari S, Fossa A, Trotman J, Molin D, d’Amore F, Enblad G, et al. long-term follow-up of the response-adjusted therapy for advanced Hodgkin lymphoma trial. J Clin Oncol. 2024;42(1):13–8.
Casasnovas RO, Bouabdallah R, Brice P, Lazarovici J, Ghesquieres H, Stamatoullas A, et al. Positron emission tomography–driven strategy in advanced Hodgkin lymphoma: prolonged follow-up of the AHL2011 Phase III Lymphoma Study Associationstudy. J Clin Oncol. 2022;40(10):1091–101.
Connors JM, Jurczak W, Straus DJ, Ansell SM, Kim WS, Gallamini A, et al. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin’s lymphoma. N Engl J Med. 2018;378(4):331–44.
Herrera AF, LeBlanc M, Castellino SM, Li H, Rutherford SC, Evens AM, et al. Nivolumab+AVD in advanced-stage classic Hodgkin’s lymphoma. N Engl J Med. 2024;391(15):1379–89.
Borchmann P, Ferdinandus J, Schneider G, Moccia A, Greil R, Hertzberg M, et al. Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomised, multicentre, parallel, open-label, phase 3 trial. Lancet. 2024;404(10450):341–52.
Chen R, Zinzani PL, Fanale MA, Armand P, Johnson NA, Brice P, et al. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin lymphoma. J Clin Oncol. 2017;35(19):2125–32.
Armand P, Engert A, Younes A, Fanale M, Santoro A, Zinzani PL, et al. Nivolumab for relapsed/refractory classic Hodgkin Lymphoma after failure of autologous hematopoietic cell transplantation: extended follow-up of the multicohort single-arm Phase II CheckMate 205 trial. J Clin Oncol. 2018;36(14):1428–39.
Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol. 2012;30(18):2183–9.
Kuruvilla J, Ramchandren R, Santoro A, Paszkiewicz-Kozik E, Gasiorowski R, Johnson NA, et al. Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study. Lancet Oncol. 2021;22(4):512–24.
Rutherford SC, Li H, Herrera AF, LeBlanc M, Ahmed S, Davison K, et al. Nivolumab-AVD Versus brentuximab vedotin–AVD in older patients with advanced-stage classic Hodgkin lymphoma enrolled on S1826. J Clin Oncol. 2025;0(0):JCO-25-00204.
Bröckelmann PJ, Bühnen I, Meissner J, Trautmann-Grill K, Herhaus P, Halbsguth TV, et al. Nivolumab and doxorubicin, vinblastine, and dacarbazine in early-stage unfavorable Hodgkin lymphoma: final analysis of the randomized German Hodgkin Study Group Phase II NIVAHL trial. J Clin Oncol. 2023;41(6):1193–9.
Fornecker LM, Lazarovici J, Aurer I, Casasnovas RO, Gac AC, Bonnet C, et al. Brentuximab vedotin plus AVD for first-line treatment of early-stage unfavorable Hodgkin lymphoma (BREACH): a multicenter, open-label, randomized, phase II trial. J Clin Oncol. 2023;41(2):327–35.
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Hodgkin lymphoma. [Internet]. National Comprehensive Cancer Network; 2025 [cited 2025 Jun 19]. Available from: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1439
Cheng PTM, Villa D, Gerrie AS, Freeman CL, Slack GW, Gascoyne RD, et al. The outcome of older adults with classic Hodgkin lymphoma in British Columbia. Blood Adv. 2022;6(22):5924–32.
Evens AM, Connors JM, Younes A, Ansell SM, Kim WS, Radford J, et al. Older patients (aged ≥60 years) with previously untreated advanced-stage classical Hodgkin lymphoma: a detailed analysis from the phase III ECHELON-1 study. Haematologica. 2021;107(5):1086–94.
Evens AM, Hong F, Gordon LI, Fisher RI, Bartlett NL, Connors JM, et al. The efficacy and tolerability of ABVD and Stanford V in older Hodgkin lymphoma patients: a comprehensive analysis from the North American Intergroup Trial E2496. Br J Haematol. 2013;161(1):76–86.
Evens AM, Advani RH, Helenowski IB, Fanale M, Smith SM, Jovanovic BD, et al. Multicenter phase II Study of sequential brentuximab vedotin and doxorubicin, vinblastine, and dacarbazine chemotherapy for older patients with untreated classical Hodgkin lymphoma. J Clin Oncol. 2018;36(30):3015–22.
Ferdinandus J, Kaul H, Fosså A, Hüttmann A, Keil F, Ko YD, et al. PET-guided brecadd in older patients with advanced-stage classic Hodgkin lymphoma: results of the phase 2 part of the GHSG HD21 trial. Blood. 2024;144(Supplement 1):568.
Rutherford SC, Li H, Herrera AF, Leblanc M, Ahmed S, Davison KL, et al. Nivolumab-AVD Is better tolerated and improves progression-free survival compared to Bv-AVD in older patients (aged ≥60 years) with advanced stage Hodgkin lymphoma enrolled on SWOG S1826. Blood. 2023;142:181.
Torka P, Feldman T, Savage KJ, Ganesan N, Drill E, Hancock H, et al. Phase II Trial of Nivolumab Plus Doxorubicin, Vinblastine, Dacarbazine as Frontline Therapy in Older Adults With Hodgkin Lymphoma. J Clin Oncol. 2025 Mar 10;43(8):985–93.
Kim JL, Villa D, Gerrie AS, Tonseth RP, Wilson D, Benard F, et al. Adolescent/ young adult (aya) patients with high-risk stage 2 classic Hodgkin lymphoma have similar outcomes to stage 3 or 4 with 6 cycles of ABVD chemotherapy. Hematol Oncol. 2025;43(S3):e128_70093.
Patrinely JR Jr, Johnson R, Lawless AR, Bhave P, Sawyers A, Dimitrova M, et al. Chronic Immune-Related Adverse Events Following Adjuvant Anti–PD-1 Therapy for High-risk Resected Melanoma. JAMA Oncol. 2021 May 1;7(5):744–8.
Armand P, Zinzani PL, Lee HJ, Johnson NA, Brice P, Radford J, et al. Five-year follow-up of KEYNOTE-087: pembrolizumab monotherapy for relapsed/refractory classical Hodgkin lymphoma. Blood. 2023 Sep 7;142(10):878–86.
Paczkowska J, Kaszkowiak M, LeBlanc M, Stewart C, Herrera AF, Fernando del Castillo JC, et al. Prognostic value of circulating tumor DNA in patients with advanced stage classic Hodgkin lymphoma treated on Swog S1826. Hematol Oncol. 2025;43(S3):e21_70093.
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Canadian Hematology Today

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.